Amides protecting groups

A more general method for preparation ofa-amino acids is the amidotnalmatesynthesis, a straightforward extension of the malonic ester synthesis (Section 22.7). The reaction begins with conversion of diethyl acetamidomalonate into an eno-late ion by treatment with base, followed by S 2 alkylation with a primary alkyl halide. Hydrolysis of both the amide protecting group and the esters occurs when the alkylated product is warmed with aqueous acid, and decarboxylation then takes place to vield an a-amino acid. For example aspartic acid can be prepared from, ethyl bromoacetate, BrCh CCHEt ... 

W Konig, R Geiger. A new amide protecting group, (methoxybenzhydryl) Chem Ber 103, 2041, 1970. 

This is protection of the amine as an amide protecting groups are discussed in the next chapter. The amino group is more nucleophilic than the phenol so it would be alkylated if we did not protect it. Protection is selective for the same reason—the amino group attacks the anhydride preferentially. Now the amide is less nucleophilic than the phenol so alkylation occurs at oxygen. You should draw mechanisms for all these steps and make sure you understand why they happen in the way that they do. 

Another useful cyclization results in the stereoselective synthesis of -lactams from thiiranium ions derived from a, -unsaturated amides. Unsaturamd amides are treated with benzenesulfenyl chloride and the product is subsequently treated with base under phase transfer conditions. The reaction legeiMiates a thiiranium ion in the presence of amide anion, which then tyclizes to form -lactams. The regiochemistry of the alkene aMtion determines the eventual stereochemical outcome e.g. cis alkenes produce c(5- -lactams Scheme 2). The yields of the cyclization products are quite sensitive to the amide-protecting group which was enqtloyed. With 4-anisyl amide the yield is modoate (73%), but wdth 4-nitr henyl amide the yield is excellent (97%), suggesting that the amide must be deprotonated before cyclization can occur. 

Table 1 Removal of Amide Protecting Groups under Addolytic Conditions " ...

Amidazolidine protecting groups, 493 Amide protecting groups (in crab-like synthesis), 146, 150. 365. 799. 800... 

The introduction of the primary amide-protecting group is straightforward and generally involves acid-catalyzed reaction of the corresponding... 

The 2-hydroxybenzyl (Hbz) amide protecting group has been evaluated for use in Boc SPPS because it is stable to TFA but labile to TFSMA. To date, ACP (65-74) is the only reported synthesis using Hbz protection [214]. A comparison of sequences prepared using optimized Boc chemistry and Fmoc chemistry with Hmb backbone protection showed no significant difference between these two methods [205]. 

Amide-protecting groups, protecting groups for C-terminal amides of amino... 

Scheme 14. Use of a benzyl amide protecting group prevents the formation of a ,...

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